Alexander Betts

Contrasted coevolutionary dynamics between a bacterial pathogen and its bacteriophages

Significance Scientists have long debated the dynamic form of perpetual reciprocal adaptations, or coevolution, between hosts and their parasites. The two main types of antagonistic coevolution described to date are arms race dynamics, in which interaction traits escalate through time, and fluctuating selection dynamics, in which traits cycle through time. We used experimental evolution between Pseudomonas aeruginosa and a panel of its lytic phages and found the full known range of coevolutionary dynamics. We argue that the coevolutionary pattern is determined by whether phages typically adsorb directly to receptors on the bacterial outer membrane or instead use retractable type IV pili as a primary or alternative site. Our results have applications in the use of phages as therapeutics or disinfectants to control bacterial pathogens. Many antagonistic interactions between hosts and their parasites result in coevolution. Although coevolution can drive diversity and specificity within species, it is not known whether coevolutionary dynamics differ among functionally similar species. We present evidence of coevolution within simple communities of Pseudomonas aeruginosa PAO1 and a panel of bacteriophages. Pathogen identity affected coevolutionary dynamics. For five of six phages tested, time-shift assays revealed temporal peaks in bacterial resistance and phage infectivity, consistent with frequency-dependent selection (Red Queen dynamics). Two of the six phages also imposed additional directional selection, resulting in strongly increased resistance ranges over the entire length of the experiment (ca. 60 generations). Cross-resistance to these two phages was very high, independent of the coevolutionary history of the bacteria. We suggest that coevolutionary dynamics are associated with the nature of the receptor used by the phage for infection. Our results shed light on the coevolutionary process in simple communities and have practical application in the control of bacterial pathogens through the evolutionary training of phages, increasing their virulence and efficacy as therapeutics or disinfectants.

Rapid evolution of microbe-mediated protection against pathogens in a worm host.

Microbes can defend their host against virulent infections, but direct evidence for the adaptive origin of microbe-mediated protection is lacking. Using experimental evolution of a novel, tripartite interaction, we demonstrate that mildly pathogenic bacteria (Enterococcus faecalis) living in worms (Caenorhabditis elegans) rapidly evolved to defend their animal hosts against infection by a more virulent pathogen (Staphylococcus aureus), crossing the parasitism–mutualism continuum. Host protection evolved in all six, independently selected populations in response to within-host bacterial interactions and without direct selection for host health. Microbe-mediated protection was also effective against a broad spectrum of pathogenic S. aureus isolates. Genomic analysis implied that the mechanistic basis for E. faecalis-mediated protection was through increased production of antimicrobial superoxide, which was confirmed by biochemical assays. Our results indicate that microbes living within a host may make the evolutionary transition to mutualism in response to pathogen attack, and that microbiome evolution warrants consideration as a driver of infection outcome.

Silk route to the acceptance and re-implementation of bacteriophage therapy

This multidisciplinary expert panel opinion on bacteriophage therapy has been written in the context of a society that is confronted with an ever-increasing number of antibiotic resistant bacteria. To avoid the return to a pre-antibiotic era, alternative treatments are urgently needed. The authors aim to contribute to the opinion formation of relevant stakeholders on how to potentially develop an infrastructure and legislation that paves the way for the acceptance and re-implementation of bacteriophage therapy.

Host and Parasite Evolution in a Tangled Bank

Most hosts and parasites exist in diverse communities wherein they interact with other species, spanning the parasite-mutualist continuum. These additional interactions have the potential to impose selection on hosts and parasites and influence the patterns and processes of their evolution. Yet, host-parasite interactions are almost exclusively studied in species pairs. A wave of new research has incorporated a multispecies community context, showing that additional ecological interactions can alter components of host and parasite fitness, as well as interaction specificity and virulence. Here, we synthesize these findings to assess the effects of increased species diversity on the patterns and processes of host and parasite evolution. We argue that our understanding of host-parasite interactions would benefit from a richer biotic perspective.

Parasite diversity drives rapid host dynamics and evolution of resistance in a bacteria-phage system.

Host–parasite evolutionary interactions are typically considered in a pairwise species framework. However, natural infections frequently involve multiple parasites. Altering parasite diversity alters ecological and evolutionary dynamics as parasites compete and hosts resist multiple infection. We investigated the effects of parasite diversity on host–parasite population dynamics and evolution using the pathogen Pseudomonas aeruginosa and five lytic bacteriophage parasites. To manipulate parasite diversity, bacterial populations were exposed for 24 hours to either phage monocultures or diverse communities containing up to five phages. Phage communities suppressed host populations more rapidly but also showed reduced phage density, likely due to interphage competition. The evolution of resistance allowed rapid bacterial recovery that was greater in magnitude with increases in phage diversity. We observed no difference in the extent of resistance with increased parasite diversity, but there was a profound impact on the specificity of resistance; specialized resistance evolved to monocultures through mutations in a diverse set of genes. In summary, we demonstrate that parasite diversity has rapid effects on host–parasite population dynamics and evolution by selecting for different resistance mutations and affecting the magnitude of bacterial suppression and recovery. Finally, we discuss the implications of phage diversity for their use as biological control agents.

Adding biotic complexity alters the metabolic benefits of mutualism.

Mutualism is ubiquitous in nature and plays an integral role in most communities. To predict the eco‐evolutionary dynamics of mutualism it is critical to extend classic pair‐wise analysis to include additional species. We investigated the effect of adding a third species to a pair‐wise mutualism in a spatially structured environment. We tested the hypotheses that selection for costly excretions in a focal population (i) decreases when an exploiter is added (ii) increases when a third mutualist is added relative to the pair‐wise scenario. We assayed the selection acting on Salmonella enterica when it exchanges methionine for carbon in an obligate mutualism with an auxotrophic Escherichia coli. A third bacterium, Methylobacterium extorquens, was then added and acted either as an exploiter of the carbon or third obligate mutualist depending on the nitrogen source. In the tripartite mutualism M. extorquens provided nitrogen to the other species. Contrary to our expectations, adding an exploiter increased selection for methionine excretion in S. enterica. Conversely, selection for cooperation was lower in the tripartite mutualism relative to the pair‐wise system. Genome‐scale metabolic models helped identify the mechanisms underlying these changes in selection. Our results highlight the utility of connecting metabolic mechanisms and eco‐evolutionary dynamics.

Network structure and local adaptation in coevolving bacteria-phage interactions

Numerous theoretical and experimental studies have investigated antagonistic co‐evolution between parasites and their hosts. Although experimental tests of theory from a range of biological systems are largely concordant regarding the influence of several driving processes, we know little as to how mechanisms acting at the smallest scales (individual molecular and phenotypic changes) may result in the emergence of structures at larger scales, such as co‐evolutionary dynamics and local adaptation. We capitalized on methods commonly employed in community ecology to quantify how the structure of community interaction matrices, so‐called bipartite networks, reflected observed co‐evolutionary dynamics, and how phages from these communities may or may not have adapted locally to their bacterial hosts. We found a consistent nested network structure for two phage types, one previously demonstrated to exhibit arms race co‐evolutionary dynamics and the other fluctuating co‐evolutionary dynamics. Both phages increased their host ranges through evolutionary time, but we found no evidence for a trade‐off with impact on bacteria. Finally, only bacteria from the arms race phage showed local adaptation, and we provide preliminary evidence that these bacteria underwent (sometimes different) molecular changes in the wzy gene associated with the LPS receptor, while bacteria co‐evolving with the fluctuating selection phage did not show local adaptation and had partial deletions of the pilF gene associated with type IV pili. We conclude that the structure of phage–bacteria interaction networks is not necessarily specific to co‐evolutionary dynamics, and discuss hypotheses for why only one of the two phages was, nevertheless, locally adapted.

High parasite diversity accelerates host adaptation and diversification

Between bacteria and phages, increasing phage diversity accelerates arms races with the host and leads to increased bacterial divergence. Multiple parasites speed host evolution Virtually all organisms are parasitized by multiple species, but our current understanding of host-parasite interactions is based on pairwise species interactions. Betts et al. address this by using the bacterium Pseudomonas aeruginosa and five different phage virus parasites. Increasing parasite diversity accelerated the rate of host evolution, driving both faster genomic evolution within populations and greater divergence between populations. Thus, different parasite loads prompt different evolutionary dynamics and profoundly shape host evolution by different mechanisms. Science, this issue p. 907 Host-parasite species pairs are known to coevolve, but how multiple parasites coevolve with their host is unclear. By using experimental coevolution of a host bacterium and its viral parasites, we revealed that diverse parasite communities accelerated host evolution and altered coevolutionary dynamics to enhance host resistance and decrease parasite infectivity. Increases in parasite diversity drove shifts in the mode of selection from fluctuating (Red Queen) dynamics to predominately directional (arms race) dynamics. Arms race dynamics were characterized by selective sweeps of generalist resistance mutations in the genes for the host bacterium’s cell surface lipopolysaccharide (a bacteriophage receptor), which caused faster molecular evolution within host populations and greater genetic divergence among populations. These results indicate that exposure to multiple parasites influences the rate and type of host-parasite coevolution.

Integrative analysis of fitness and metabolic effects of plasmids in Pseudomonas aeruginosa PAO1

Horizontal gene transfer (HGT) mediated by the spread of plasmids fuels evolution in prokaryotes. Although plasmids provide bacteria with new adaptive genes, they also produce physiological alterations that often translate into a reduction in bacterial fitness. The fitness costs associated with plasmids represent an important limit to plasmid maintenance in bacterial communities, but their molecular origins remain largely unknown. In this work, we combine phenomics, transcriptomics and metabolomics to study the fitness effects produced by a collection of diverse plasmids in the opportunistic pathogen Pseudomonas aeruginosa PAO1. Using this approach, we scan the physiological changes imposed by plasmids and test the generality of some main mechanisms that have been proposed to explain the cost of HGT, including increased biosynthetic burden, reduced translational efficiency, and impaired chromosomal replication. Our results suggest that the fitness effects of plasmids have a complex origin, since none of these mechanisms could individually provide a general explanation for the cost of plasmid carriage. Interestingly, our results also showed that plasmids alter the expression of a common set of metabolic genes in PAO1, and produce convergent changes in host cell metabolism. These surprising results suggest that there is a common metabolic response to plasmids in P. aeruginosa PAO1.